A microfluidic dermal fibroblast-macrophage co-culture on a chip linking inflammatory signalling to barrier-associated function.

Abstract

Here, we report a microfluidic dermal fibroblast-macrophage co-culture on-chip that directly links macrophage-driven inflammatory signalling to dermal barrier function within a three-dimensional collagen microenvironment. The platform integrates spatially compartmentalized co-culture of dermal fibroblasts and macrophages separated by a micropillar-confined collagen type I matrix, enabling non-contact paracrine communication while preserving extracellular matrix (ECM) architecture. Upon lipopolysaccharide stimulation, the system rapidly reproduced of acute inflammation within 6 h and 12 h, including elevated nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) secretion, increased permeability to both 10 kDa and 70 kDa FITC-dextran, and disruption of fibronectin organization. The measured permeability coefficient closely matched reported <i>in vivo</i> skin values, supporting physiological relevance. Suppression of inflammatory mediators using a nanostructured lipid carrier encapsulating <i>Zingiber cassumunar</i> and <i>Kaempferia parviflora</i> extracts resulted in dose-dependent reductions in NO and TNF-α, accompanied by restoration of dermal thickness and ECM integrity. Importantly, biochemical inhibition of macrophage activation translated into structural recovery of the fibroblast-embedded matrix, demonstrating a clear coupling between immune signalling and tissue-level remodeling. This microfluidic platform provides a rapid, physiologically relevant, and animal-free system for mechanistic investigation of dermal inflammation and evaluation of anti-inflammatory therapeutics.